ECJ: notification of carve-out for the patented indications in SmPC and PIL by a generic producer limits the scope of the MA

On 14 February 2019, the European Court of Justice (ECJ) published its preliminary ruling related to the policy of the Dutch Medicines Evaluation Board (College ter Beoordeling van Geneesmiddelen – CBG) concerning the limitation of a market authorisation (MA) upon a request of a generic producer for a carve-out of the patented indications in the Summary of Product Characteristics (SmPC) and Patient Information Leaflet (PIL). This ruling was handed down in the context of Warner-Lambert’s enforcement of its Lyrica patent that contains second medical use claims for the use of pregabalin for manufacturing a medicine for the treatment of (neuropathic) pain. This means that pregabalin could be freely used for the non-patented indication, but generic manufacturers had to avoid that pregabalin would be used for the patented indication (neuropatic) pain.

Request by the Dutch Court of Appeal for a preliminary ruling

The Dutch Court of Appeal (CoA) in The Hague had asked several questions to the ECJ in 2017. The issue before the CoA was the following. Producers of generic medicinal products generally apply for a market authorisation (MA) in the abridged MA authorisation procedure (article 10 of the Directive relating to medicinal products for human use (2001/83/EC) – the Directive). In that procedure, they only have to refer to a bioequivalent reference product, which exempts them of having to submit results of (pre-)clinical tests. Pursuant to article 11 of the Directive, applicants and holders of such MA for a generic medicine can carve out a patented indication in de SmPC and PIL in order to prevent infringement of second medical use claims, while allowing these generic producers to already enter the market for the non-patented indications.

Holders typically notify the relevant national authorities (in the Netherlands, the CBG) of such desired carve-out, so that the authorities also carve out the patented indications in the SmPC and PIL that they publish online. However, after a carve-out notification, the CBG does not carve out the patented indication in the PIL and SmPC on its website. The CBG even requires the holder of the market authorization to refer to the online SmPC and PIL in the paper versions as a means to direct patients and other users to the complete information on the medicine. According to the CBG, this information is necessary in order to prevent confusion of patients about possible indications, for example if they read about other indications on the internet.

Because of this policy, downstream users of a generic product can easily find the patented indication of the generic substance. According to Warner-Lambert, this facilitates the ultimate use of the generic medicine for the patented indication, and therefore enhances the likelihood of infringement. Some generic producers have asked the CBG to carve out the patented indication in the online versions of the SmPC and PIL, which the CBG has refused. The CBG is the only European authority that refuses to publish a carved-out SmPC and PIL.

In first instance, the District Court of The Hague held the CBG liable under the civil law of tort, because Warner-Lambert is likely to suffer damages as a result of this policy. The argument relating to the confusion of patients was dismissed, because – in the view of the Court – other measures can be taken to prevent this confusion. In appeal, the parties agree that Article 11 of the Directive allows a carve-out in the SmPC and PIL, but their positions differ as to the consequences of a notification to the CBG (or another relevant authority). According to Warner-Lambert, the notification by a holder of a MA for a generic medicine is in fact a request to limit the MA to the non-patented indication. As a consequence of this, the CBG should publish the SmPC and PIL with a carve-out. On the other hand, the CBG is of the opinion that a carve-out by the generic does not have any consequences for the market authorization. The CoA has asked three questions to the ECJ about the interpretation of Article 11.

1. Is the correct interpretation of Article 11 of the Directive (or any other European law provision) that the notification by a holder of a market authorization for a generic medicine not to include a patented indication in the PIL or SmPC is in fact a request to limit the market authorization to the non-patented indication?
2. If the answer to question 1 is negative, do Article 11 and 21(3) of the Directive (or any other European law provision) preclude that the relevant authority publishes a patented indication in the PIL and SmPC after a notification as stated in question 1?
3. Does the answer to question 2 change if the relevant authority requires the holder of the market authorization to refer to the online SmPC and PIL – including a patented indication　 – in the paper version of the SmPC and PIL?

Ruling ECJ

With regard to the first question, the ECJ explained that in the abridged procedure, the indications of the generic product for which an MA is applied must correspond to the indications covered by the MA for the reference product. This means that the indications that are included in the SmPC and PIL of the generic product and the reference product should also correspond. Article 11 of the Directive provides for an exception to this principle, by allowing a carve-out of the patented indication in the SmPC and PIL. As we described above, the ECJ sets out that the rationale behind this exception is not to delay the entry on the market of generic products until expiry of all patents relating to other (still patented) indications for which the reference medical product can be used.

If the applicant of an MA in the abridged procedure makes use of the exception in article 11 of the Directive, the so-granted MA will only be valid with regard to the non-patented indications. Therefore, if an applicant submits an SmPC and PIL without the patented indications, this should be interpreted as a limitation of the MA application to these non-patented indications (article 8(3)(j) in connection with article 11 of the Directive). The competent authority does not have any discretion in that respect.

This interpretation is not affected by the fact that the MA holder will be required to request a variation of the MA for its generic product, when it wishes the MA to also cover another indication upon the expiration of the patent for this indication. Such request is governed by article 10 of Regulation 1234/2008 .

Therefore, the notification not to include a patented indication in the SmPC or PIL by an applicant or holder of an MA for a generic medicinal product to the competent national authority is in fact a request to limit the scope of the MA to the non-patented indication. As the ECJ answered the first question affirmative, there was no need to answer the two other questions.

It is interesting to see how the ECJ approaches these questions at a time when there is an active debate about how much a generic should do to prevent infringement of a second medical use patent, following the decision in the Dutch Sun/Novartis (see our previous blog post: "Dutch Supreme Court rules on indirect infringement of Novartis' Swiss-type claim") and MSD/Teva case (see our previous blog post: "Dutch Supreme Court ends second medical use confusion... for now"). The policy of the CBG might have to change following the answers of the ECJ, making it easier for generic producers not to infringe a second medical use patent. The Dutch CoA will likely hand down its final ruling on the policy of the CBG in the upcoming months.